crossing96/oncoscreening huggingface dataset:
Chronic lymphocytic leukaemia, synchronous small cell carcinoma and squamous neoplasia of the urinary bladder in a paraplegic man following long-term phenoxybenzamine therapy.	STUDY DESIGN: A case report. OBJECTIVE: To raise awareness among spinal cord clinicians of the possible carcinogenic effect of phenoxybenzamine and of the rare occurrence of small cell carcinoma in the neuropathic bladder. SETTING: Regional Spinal Injuries Centre and District General Hospital, Southport, Merseyside, United Kingdom. CASE REPORT: A 28-year-old man sustained a fracture dislocation of L-1 with consequent paraplegia (ASIA impairment scale A). Phenoxybenzamine treatment enabled his indwelling catheter to be discarded in favour of a penile sheath, but it caused unacceptable dizziness and was stopped after 7 years. After 20 years, he developed chronic lymphocytic leukaemia, which was treated with chlorambucil and fludarabine. After 2 years, investigation of bilateral hydronephrosis revealed a primary small cell carcinoma of the bladder with coexistent squamous dysplasia. Uraemia supervened and, declining active treatment, the patient died 3 weeks after diagnosis. CONCLUSION: Phenoxybenzamine, a known carcinogen in rodents, is likely also to be carcinogenic in humans, and patients with spinal cord injury who have received the drug for any significant period of time, need close follow-up to allow early detection of cancer. Phenoxybenzamine should not be prescribed on a long-term basis, and should instead be replaced with a selective alpha-blocker.	bladder
Results of second-look resection after primary resection of T1 tumour of the urinary bladder.	OBJECTIVE: To study residual tumours at second-look resection in patients resected 4-8 weeks earlier for T1 tumours of the urinary bladder. MATERIAL AND METHODS: All patients randomized in the ongoing Nordic T1G2-G3 Bladder Sparing Study with monitored data available were included in the study. Data on residual tumours at second-look resection were compared to basic patient and tumour characteristics. RESULTS: There were 72 patients (56%) without and 57 with residual exophytic tumours. In the former group, 20 patients (28%) had carcinoma in situ, compared to 19 (33%) in the latter group. Potentially dangerous tumours (either carcinoma in situ, T1 or Ta grade 3) were observed in 55 patients (43%). Multiple tumours at primary resection were more prone to residual tumour at second-look resection than single tumours. No other tumour or patient characteristics could predict the occurrence of a residual tumour. CONCLUSIONS: Residual tumours are frequently observed at second-look resection 4-8 weeks after primary resection of T1 tumours. The majority of residual tumours detected at this stage are potentially dangerous; therefore, early second-look resection followed by intravesical instillation therapy is mandatory in patients with T1 tumours of the urinary bladder.	bladder
Detection of chromosomal alterations in bladder transitional cell carcinomas from Northern China by comparative genomic hybridization.	To identify chromosome alterations in Chinese bladder cancer, forty-six transitional cell carcinomas of the bladder were analyzed by comparative genomic hybridization. Frequent gains of DNA copy number were observed on 1p (13/46), 1q (13/46), 5p (8/46), 6p (9/46), 7p (7/46), 8q (12/46), 11q (8/46), 17q (11/46), 19q (7/46), 20q (8/46) and Yq (8/46), with minimal overlapping regions at 1p32-pter (10/46), 1q21-q24 (12/46), 5p (8/46), 6p22-p23 (7/46), 7p11.2-p14 (7/46), 8q22-q24 (12/46), 11q13-q14 (8/46), 17q22-qter (11/46), 19q11-13.2 (7/46), 20q11-q13.2 (8/46) and Yq11 (8/46). Losses were predominantly found on 2q (16/46), 5q (8/46), 8p (7/46), 9p (8/46), 9q (13/46), 11p (7/46), 13q (7/46), 17p (12/46), 18q (7/46), Xp (18/46) and Xq (19/46), with smallest overlapping regions at 2q32-qter (16/46), 5q12-q31 (8/46), 8p12-pter (7/46), 9p21-pter (10/46), 9q (13/46), 11p (7/46), 13q13-q22 (7/46), 17p (12/46), 18q21-qter (7/46), Xp (18/46) and Xq (19/46). There were significantly higher frequencies of gains of 1q21-q24 and 17q22-qter in moderately differentiated tumors as compared with those in well-differentiated tumors, indicating a possible association of these two abnormalities with the dedifferentiation of tumor cells. Gains of 1p32-pter, 5p, 6p22-p23, 11q13-q14, 17q22-qter and losses of 2q32-qter, 9q, 17p were more frequent in pT1 as compared with those in pTa carcinomas. Gains at 1q21-q24, 7p11.2-p14, 8q22-q24, 19q, 20q11-q13.2 and losses at 5q12-q31, 8p12-pter, 9p21-pter, 11p, 13q13-q22 and 18q21-qter were unique to pT1 and higher stage tumors, suggesting that genes responsible for the invasion and progression of bladder cancer might be located at these chromosomal regions. In multiple tumors from the same patients, consistent alterations such as gains of 8q, 11q13-q14, 12q13-q15, 13q12, 20q and losses of 2q32-qter, 8p, 9, 11p, 11q21-qter, 13q13-qter, X were detected. These abnormalities were possibly earlier events, which might play a critical role during the genesis of the tumors. Further detailed studies to the recurrent aberration regions may lead to the identification of oncogenes and tumor suppressor genes involved in the development and progression of Chinese bladder cancer.	bladder
The use of risk estimation models for the induction of secondary cancers following radiotherapy.	Theoretical predictions of cancer risk from radiotherapy may be used as a complementary criterion for the selection of successful treatment plans together with the classical approach of estimating the possible deterministic effects. However, any such attempts must take into consideration the specific features of radiation treatment. This paper explores several possible methods for estimating the risk of cancer following radiotherapy in order to investigate the influences of the fractionation and the non-uniformity of the dose to the irradiated organ. The results indicate that dose inhomogeneity plays an important role in predicting the risk for secondary cancer and therefore for predictive purposes it must be taken into account through the use of the dose volume histograms. They also suggest that the competition between cell killing and the induction of carcinogenic mutations has to be taken into consideration for more realistic risk estimations. Furthermore, more realistic parameters could be obtained if this competition is also included in analyses of epidemiological data from radiotherapy applications.	bladder
Lymphovascular invasion is independently associated with overall survival, cause-specific survival, and local and distant recurrence in patients with negative lymph nodes at radical cystectomy.	PURPOSE: We hypothesized that bladder cancer patients with associated lymphovascular invasion (LVI) are at increased risk of occult metastases. METHODS: A multi-institutional group (University of Texas Southwestern [Dallas, TX], Baylor College of Medicine [Houston, TX], Johns Hopkins University [Baltimore, MD]) carried out a retrospective study of 958 patients who underwent cystectomy for bladder cancer between 1984 and 2003. Of patients with transitional-cell carcinoma (n = 776), LVI status was available for 750. LVI was defined as the presence of tumor cells within an endothelium-lined space. RESULTS: LVI was present in 36.4% (273 of 750) overall, involving 26% (151 of 581) and 72% (122 of 169) of node-negative and node-positive patients, respectively. Prevalence of LVI increased with higher pathologic stage (9.0%, 23%, 60%, and 78%, for T1, T2, T3, and T4, respectively; P < .001). Using multivariate Cox regression analyses including age, stage, grade, and number of pelvic lymph nodes removed, LVI was an independent predictor of local (HR = 2.03, P = .049), distant (HR = 2.60, P = .0011), and overall (HR = 2.02, P = .0003) recurrence in node-negative patients. LVI was an independent predictor of overall (HR = 1.84, P = .0002) and cause-specific (HR = 2.07, P = .0012) survival in node-negative patients. LVI maintained its independent predictor status in competing risks regression models (P = .013), where other-cause mortality was considered as a competing risk. LVI was not a predictor of recurrence or survival in node-positive patients. CONCLUSION: LVI is an independent predictor of recurrence and decreased cause-specific and overall survival in patients who undergo cystectomy for invasive bladder cancer and are node-negative. These patients represent a high risk group that may benefit from integrated therapy with cystectomy and perioperative systemic chemotherapy.	bladder
Minichromosome maintenance proteins 2 and 5 expression in muscle-invasive urothelial cancer: a multivariate survival study including proliferation markers and cell cycle regulators.	Evaluation of cell cycle regulators has gained special interest in the effort to increase the amount of prognostic information in malignant tumors. Minichromosome maintenance proteins (MCMs) drive the formation of prereplicative complexes, which is the first key event during G1 phase. Therefore, altered MCM expression may be a hallmark of cell cycle deregulation, which is supposed to be the most essential mechanism in the development and progression of bladder cancer. Our aim was to investigate the value of MCMs as proliferation markers and prognostic indicators in detrusor muscle-invasive urothelial bladder carcinomas. We analyzed immunohistochemically the expression of MCM-2 and MCM-5 in 65 patients with detrusor muscle-invasive urothelial bladder carcinomas in relation with clinicopathologic parameters, patients' overall and disease-free survival, and the expression of the conventional proliferation index Ki-67 and other cell cycle modulators (p53, pRb, p21(WAF1), and p27(Kip1)). The levels of MCM-2 and MCM-5 were significantly higher in high-grade (P < .0001), advanced-stage (P = .001), and nonpapillary tumors (P < .0001). The expression of MCM-2 and MCM-5 significantly associated with the conventional proliferation index Ki-67 (P = .0001 for each protein). The expression of MCM-2 or MCM-5 positively correlated with p53 labeling index (P = .014 and P = .009, respectively). Also, median p21(WAF1) labeling index was higher in MCM-5 high expressors (P = .028). Finally, both MCM-2 and MCM-5 associated significantly with adverse patients' outcome in both univariate (P = .0072 and P = .0074, respectively) and multivariate (P = .0001) analysis. In conclusion, MCM-2 and MCM-5 appear to be reliable proliferation indexes and useful prognostic markers in patients with muscle-invasive urothelial bladder carcinomas.	bladder
[Follow up of urinary bladder cancer--a task for the urology nurse?].	The introduction of the flexible cystoscope has simplified the examination for both the patient and the examiner. With an attached video camera to the cystoscope it showed that the assistent nurse fastly learned to interpret any finding in the bladder. In an article from England it was shown that a trained nurse cystoscopist had the same accuracy in detecting bladder tumors as a consultant urologist. The present study addresses the question if the same is valid in our department. After a period of training we started the study. 50 consecutive patients with known bladder cancer were first examined by the nurse who recorded any relapses of bladder tumor. Then the urologist examined the bladder unaware of the nurse's finding. Any discrepancy was reexamined together. 23 relapse cases of tumor were found, all which were diagnosed by the nurse. The urologist was un-able to detect 2 small grade 1 tumors. The result strengthened us to initiate a nurse-led follow up of patients with known bladder tumor. Until now about 100 cystoscopies have been done by a nurse with only good experience.	bladder
Growth inhibition efficacy of an adenovirus expressing dual therapeutic genes, wild-type p53, and anti-erbB2 ribozyme, against human bladder cancer cells.	The altered expression of both p53 and erbB2 is strongly related to the disease status and the outcome of bladder cancers. We examined the antitumor efficacy by the modulation of these genetic alterations with a newly designed dual-gene-expressing adenovirus (Ad-p53/erbB2Rz), which expresses p53 and anti-erbB2 ribozyme simultaneously in human bladder cancer cells. Cell growth inhibition efficacy along with biological responses of this virus was compared with other viral vectors (Ad-p53, which expresses wild-type p53 cDNA, and Ad-erbB2Rz, which expresses anti-erbB2 ribozyme, solely or in combination). Sufficient transgene expression in targeted cells and the altered expression of the targeted genes and their encoded proteins were obtained by each therapeutic vector. Each of the three therapeutic viral vectors inhibited bladder cancer cell growth, and the putative additive antitumor effect was shown by the combination of two of the therapeutic vectors. Furthermore, Ad-p53/erbB2Rz had superior therapeutic efficacy when the same titers of viruses were infected. Nonspecific vector-related toxicity was minimized by reducing the total amount of viral titers by using the dual-gene-expressing adenovirus. Modulation of multiple genetic abnormalities might enhance the therapeutic efficacy, and vector-related toxicity could be minimized when the total amount of viral titers are reduced.	bladder
Epigenetic inactivation of SFRP genes and TP53 alteration act jointly as markers of invasive bladder cancer.	In the United States each year, almost 13,000 deaths are attributable to bladder cancer, with the majority of these deaths related to higher stage, muscle-invasive solid tumors. Epigenetic silencing of the secreted frizzled receptor proteins (SFRP), antagonists of the WNT pathway, leads to constitutive WNT signaling, altering cell morphology and motility. Identifying alterations in this pathway in bladder cancer may prove useful for defining the invasive phenotype and provide targets for guiding therapy. Using a population-based study of bladder cancer (n = 355), we examined epigenetic alterations, specifically gene promoter hypermethylation, of four SFRP genes in addition to immunohistochemical staining of TP53, which has been previously shown to be a predictor of invasive disease. We observed a significant linear trend (P < 0.0004) in the magnitude of the risk of invasive disease with the number of SFRP genes methylated. Both TP53 alteration and SFRP gene methylation showed significant independent associations with invasive bladder cancer. Strikingly, in examining the joint effect of these alterations, we observed a >30-fold risk of invasive disease for patients with both altered SFRP gene methylation and intense TP53 staining (odds ratio, 32.1; P < 10(-13)). Overall patient survival was significantly poorer in patients with any SFRP genes methylated (P < 0.0003) and in proportional hazards modeling, patients with methylation of any SFRP gene had significantly poorer overall survival (hazard ratio, 1.78; P < 0.02) controlled for TP53 staining intensity and other survival-associated factors. Classifying tumors based on SFRP methylation status and TP53 protein staining intensity may be a clinically powerful predictor of invasive, deadly disease.	bladder
Urinary bladder carcinoma and human papilloma virus infection, an appraisal of risk.	Human papilloma virus (HPV) is a well known risk factor for cancer development in different body sites, involved in the pathogenesis of several intraepithelial lesions and cancers, for example of the upper alimenatry and respiratory tracts and cervix. Urinary bladder carcinoma is a common urological malignancy for which a relationship with human HPV has been indicated, but the results are controversial. Here, the author performed an appraisal of the previous reports on the studies to document correlation between HPV infection, defined as DNA positive, and urinary bladder carcinoma. According to the literature review, 5 reports were recruited for metanalysis, including 239 cases and 52 healthy subjects. The overall HPV DNA positive rates for the patients and healthy control subjects were 25.5 % (61/239) and 11.5 % (6/52), respectively, the odds ratio of 2.6 pointing to potential as a risk factor.	bladder
Differential diagnosis and evaluation of the clinical course of transurethrally resected T1G3 urothelial carcinoma of the bladder by DNA image cytometry.	The value of DNA image cytometry in the differential diagnosis of 106 T1G3 urothelial carcinomas of the bladder and the long-term prognosis (recurrence-free interval, survival) of the patients was tested in comparison with Ta/T1G1 (n=30) and Ta/T1G2 carcinoma (n=54). Monolayer smears were prepared from three 50-microm-thick sections by a cell separation technique and were stained according to Feulgen. The DNA content of 250 epithelial cells, chosen at random, was determined using a TV-image analysis system CM-1 (Hund, Wetzlar, Germany). The DNA content of 30 lymphocytes served as an internal standard for the normal diploid value in every individual case. Different DNA cytometric parameters and the mean nuclear area were calculated. In comparison with G1- and G2-cases, the mean values of all DNA cytometric variables were markedly increased in the group of T1G3 cases, most obviously for the 5cEE, the mean ploidy and the ploidy imbalance (0.0006 > or = p > or = 0.0001). However, a remarkable overlay of the data distribution had to be considered. An aneuploid DNA stemline ploidy was highly characteristic for T1G3 urothelial carcinoma (sensitivity: 92%), but not sufficiently specific (57%). However, if increased values for the mean ploidy, the 2cDI, the 5cEE or the 9cEE (specificity: 86%-89%) were present additionally, the diagnosis of a T1G3 urothelial carcinoma could be made cytometrically. Follow-up data for survival (recurrence) analysis was available for 90 (82) patients of the T1G3 group. Using the median value as threshold, significant differences in survival were found for the mean ploidy only (p=0.0353). The length of the recurrence-free interval was significantly different for the entropy (p=0.0205), the 2cDI (p=0.0309) and the mean ploidy (p=0.0442). In conclusion, DNA single cell cytometry represents a highly relevant tool in the objective identification of T1G3 urothelial carcinoma of the bladder, with a sufficient sensitivity and specificity. Further, this method enables prediction of tumor recurrence if suitable variables are chosen. The long-term survival of patients with T1G3 urothelial carcinoma can be estimated by DNA cytometry only in a limited manner, possibly due to the fact that the causes of death in the mostly elderly patients will be independent from the limited tumor disease.	bladder
Effects of exogenous wild-type P16 gene transfection on the expression of cell cycle-related proteins in bladder cancer cell line.	Cell cycle regulatory proteins are important indicators in determining progression through the cell cycle. Recent experimental evidence shows that active Cdk4-Cyclin D1 complexes help cells to pass through the R point, a point of no return, after which the cells become committed to a new round of replication. It is widely known that P16INK4a can arrest cells in the G1 phase, but how the expression of exogenous P16INK4 gene can affect the activity of Cdk4-Cyclin D1 remains unclear. In this study, using exogenous wild-type P16 gene, antibodies for P16, Cdk4, Cyclin D1 and Rb proteins, and primers for these genes, we examined the expression of exogenous wild-type P16 gene and the changes of cell cycle regulatory genes (Cdk4, Cyclin D1, and Rb) in human bladder cancer cells. The cell cycle analysis revealed that the proliferation of P16 gene-transfected cancer cells was inhibited after the transfection of exogenous wild P16 gene. The immunocytochemical results indicated that after the transfection of exogenous wild-type P16 gene, the expression of Cdk4, Cyclin D1, and Rb were negative in the nuclei, whereas the expression of P16 significantly increased in the nuclei and the cytoplasm. The RT-PCR results showed that the transcription of P16 gene increased significantly after the transfection, whereas the transcription of Cdk4, Cyclin D1, and Rb decreased. Our results suggest that the transfection of exogenous wild P16 gene induces the bladder cancer cells arrested in G0/G1 phase, and the increasing expression of P16 inhibits the expression of Cdk4, Cyclin D1, and Rb in nuclei. As a consequence, exogenous P16 has negative effects on the malignant proliferation of the bladder cancer cells, and it may be considered as target for potential anticancer drugs.	bladder
[Skin metastasis from invasive bladder tumour].	Metastatic spread of advanced transitional cell bladder carcinoma rarely involves the skin. However, the presence of a skin metastasis indicates at least microscopic dissemination of cancer cells to the liver or lung, corresponding to a poor prognosis. The authors report a new case of single skin metastasis during the course of a poorly differentiated stage pT3a N0 M0 transitional cell bladder carcinoma. The patient died 5 months after the appearance of the skin metastasis.	bladder
Parental lung cancer as predictor of cancer risks in offspring: clues about multiple routes of harmful influence?	The carcinogenic effects of active smoking have been demonstrated for many sites, but the effects of passive smoking and exposures during pregnancy and breastfeeding are less well documented. We examined whether 0-70-year-old offspring of parents with lung cancer are at a risk of cancer that cannot be explained by their smoking or familial risk. It was assumed that known target sites for tobacco carcinogenesis would be affected, if any. The nationwide Swedish Family-Cancer Database with cancers recorded from 1958 to 2002 was used to calculate age-specific standardized incidence ratios (SIRs). Among offspring of affected mothers, increased risks were observed for upper aerodigestive (SIR 1.45), nasal (2.93), lung (1.71) and bladder (1.52) cancers and for kidney cancer (6.41) in one age group. The risk of bladder cancer was found in younger age groups than that of lung cancer. Cancers at many of these sites, but not the kidney or the bladder, were in excess in offspring of affected fathers. Nasal cancer was even increased when either parent was diagnosed with lung cancer; the highest risk was for nasal adenoid cystic carcinoma (7.73). The data suggest that passive smoking during childhood is associated with an increase risk of nasal cancer. For bladder and kidney cancers, a contribution by tobacco carcinogens is implicated through breastfeeding and in utero exposure.	bladder